Researchers at the ANZAC Research Institute (University of Sydney and Concord Hospital) have found the cause of a hitherto mysterious disorder causing degeneration of motor nerves that leads to severe muscle wasting in the limbs.

The disease is manifest almost exclusively in men but inherited through their mothers as carriers, a pattern that arises because the disorder is linked to a gene on the X chromosome.

Affected men cannot run properly and show loss of strength in the hands and feet becoming increasingly disabled through later life. The gene defect causes a slow, but progressive degeneration of the ends of the long motor neurons which drive the limb muscles.

The research was carried out by studying patients with this disease which has similarities with disorders like Charcot-Marie-Tooth neuropathy. While the study was led by the ANZAC Institute’s group of Professor Garth Nicholson and Dr Marina Kennerson, the work also involved collaboration with research groups in Australia, Brazil, the USA, Switzerland and Belgium.

The discovery of the gene causing this disorder produced a big surprise because it turned out to be the same gene responsible for a completely different disease, a severe, infantile multisystem disorder of copper metabolism called Menkes (kinky hair) disease.

The researchers believe the gene abnormality they have discovered causes disease by impairing the body’s ability to control copper levels and this leads to damage in the ends of extremely long motor neuron cells.

This discovery raises the potential that treatments for this disease may eventually be found. The discovery was published in the most recent edition of the American Journal of Human Genetics. The research group is based at Concord Hospital and is run by Dr. M. Kennerson in association with Professor G. Nicholson, at the ANZAC Institute. The research has been supported by grants from the National Health and Medical Research Council and the Motor Neuron Disease Research Institute of Australia.

A molecular Dr. Jekyll finally has a day job—as an electrical lineman. A new study suggests that the normal form of prion protein helps maintain the insulation that speeds electrical signals along nerve fibers.

In its twisted Mr. Hyde form, the prion protein causes fatal brain-wasting diseases, such as mad cow disease in cattle and Creutzfeldt-Jakob disease in people (SN: 8/16/08, p.20). But the normal form of the protein, which is typically found in neurons in people and other mammals, is also a good guy, a new study shows. The protein may direct cells called Schwann cells to wrap around neurons and produce myelin, a type of insulation that aids electrical communication between nerve cells. This newly discovered role for the normal form of the prion protein — designated PrP(C) or just PrP — could link the protein to nerve disorders called peripheral neuropathy, researchers led by Adriano Aguzzi, a neuropathologist at the University of Zurich, report in the Jan. 24 Nature Neuroscience.

The cells regarded as the “gate-keepers” of the barrier between blood circulation and the peripheral nerves have been hard to study and even harder to isolate. However, researchers at Baylor College of Medicine have created a laboratory model that will enable scientists to study a wide variety of diseases affecting peripheral nerves. They describe their model in the January 2010 issue of the Journal of Neuropathology and Experimental Neurology.

Specialized vascular system

“The barrier is known as the blood-nerve barrier and it regulates how peripheral nerves work. Peripheral nerves connect the central nervous system to the muscles of the limbs and sensory organs. This ‘gate keeper’ is a specialized vascular system that allows for proper nerve function by enabling the necessary nutrients in blood to flow in and unwanted material out,” said Dr. Eroboghene E. Ubogu, assistant professor of neurology and director of the Neuromuscular Immunopathology Research Laboratory at BCM.

Ubogu, who is the senior author on the study, added that very little is known about how the human blood-nerve barrier normally works or how it is altered when the peripheral nerves are diseased. The cells that make up the blood-nerve barrier are hard to study and extract because they are surrounded by a large amount of connective tissue, are present deep within the innermost layers and represent less than 1 percent of all cells found in peripheral nerves.